USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID.
Signal Transduct Target Ther
; 7(1): 7, 2022 01 04.
Article
in English
| MEDLINE | ID: covidwho-1606287
ABSTRACT
Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Signal Transduction
/
HIV-1
/
AIDS Vaccines
/
Cytidine Deaminase
/
Ubiquitin Thiolesterase
/
B-Cell Activating Factor
/
Nanoparticles
/
Ubiquitination
/
COVID-19 Vaccines
/
SARS-CoV-2
Type of study:
Experimental Studies
Topics:
Vaccines
Limits:
Animals
/
Humans
Language:
English
Journal:
Signal Transduct Target Ther
Year:
2022
Document Type:
Article
Affiliation country:
S41392-021-00858-z
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